This research project is designed to discover the mechanisms by which the microvascular lesions of diabetes mellitus are produced. The composition of normal rat glomerular basement membrane will be determined in order to establish its relationship to the collagen group of proteins and to determine whether it is similar to the renal glomerular basement membrane collagen of other species. Streptozotocin-induced diabetes mellitus will be produced in rats. Control and diabetic rats will be used to investigate the effect of abnormal carbohydrate metabolism on the chemical composition of the renal glomerular basement membrane in long-term studies. Studies of the synthesis of renal glomerular basement membrane collagen will be performed on control and diabetic rats. Experiments will inclde studies of the incorporation of proline and lysine into peptide-bound hydroxyproline and hydroxylysine and of glucose and galactose in glycosylhydroxylysine-containing compounds. The activity of the glycosyltransferase pathways will be measured in vitro. The synthesis of collagen by renal glomeruli will be studied by assay of protocollagen proline and lysine hydroxylase activity of glomerular tissue obtained from normal and diabetic (mellitus) rats. The urinary excretion of glycosylgalactosylhydroxylysine and galactosylhydroxylysine by normal humans and rats will be compared to diabetic humans and rats.